Method for reducing intracranial pressure

Abstract

The present invention relates generally to methods for reducing intracranial pressure in a subject. More particularly, the methods of the present invention include administering to the subject an effective amount of a substance P receptor antagonist.

Description

PRIORITY CLAIM[0001]This international patent application claims priority to Australian provisional patent application 2007903902 filed 19 Jul. 2007, the contents of which are herein incorporated by reference.FIELD OF THE INVENTION[0002]The present invention relates to a method for reducing intracranial pressure.BACKGROUND OF THE INVENTION[0003]A rise in intracranial pressure (ICP) is a common, life-threatening complication associated with a large number of clinical conditions. It is the primary cause of death in acute neurological conditions such as stroke, traumatic brain injury, CNS infections and neoplasia. Raised ICP is also a major complication following neurosurgical intervention, and represents a major complication and leading cause of mortality with systemic conditions such as liver failure, chronic obstructive lung disease, malaria and altitude sickness.[0004]Intracranial pressure is the pressure exerted by the contents of the cranium. The brain is encased within the skull...

AI Technical Summary

Benefits of technology

[0014]In the present studies it has been demonstrated that administration of antagonists of the substance P receptor are able to facilitate the movement of water from the brain, and thereby can reduce intracranial pressure in two animal models of brain trauma. Therefore, it is possible to reduce raised ICP, and thereby prevent or reduce the mortality and morbidity associated with this severe complication.

[0030]The present invention also provides use of a substance P receptor antagonist in the preparation of a medicament for improving the prognosis or outcome of a subject suffering from raised intracranial pressure.

Problems solved by technology

A rise in intracranial pressure (ICP) is a common, life-threatening complication associated with a large number of clinical conditions.

Raised ICP is also a major complication following neurosurgical intervention, and represents a major complication and leading cause of mortality with systemic conditions such as liver failure, chronic obstructive lung disease, malaria and altitude sickness.

However, if there is an increase in the volume of any one of the components within the cranium, this will quickly lead to complications.

Because the cranium is a rigid, closed system, it has a very limited ability to accommodate changes in volume before a rise in ICP occurs.

As ICP rises, blood perfusion and tissue oxygenation becomes difficult.

In an attempt to compensate for this, arterial vasodilation occurs in order to increase perfusion, but this leads to intracranial hypertension, which further increases the ICP.

At this stage the brain tissue begins to experience hypercapnia, and the patient rapidly deteriorates with decreasing levels of consciousness, bradycardia, dilated and sluggish pupils.

As the pressure keeps rising one gets herniation (shifts) of the brain tissue, causing ischaemia in the herniated region.

Hence, an initial small rise in ICP can trigger a vicious cycle of events that may lead to death or permanent brain damage.

In terms of therapeutic intervention, osmotic diuretics, primarily mannitol, are used to try and lower ICP, but their effectiveness is questionable.

Whilst, in theory, one would expect these agents to be able to extract fluid from brain tissue, their actual ability to do so effectively is limited.

Indeed, controlled clinical trials have shown that there are no significant clinical benefits gained by the use of osmotic diuretics.

This represents a very expensive, involved and protracted procedure, and is only occasionally done as a last-resort intervention.

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